Sequence Features, Structure, Ligand Interaction, and Diseases in Small Leucine Rich Repeat Proteoglycans

Overview

Journal J Cell Commun Signal

Date 2021 Apr 16

PMID 33860400

Citations 12

Authors

Norio Matsushima

Hiroki Miyashita

Robert H Kretsinger

Affiliations

Soon will be listed here.

Abstract

Small leucine rich repeat proteoglycans (SLRPs) are a group of active components of the extracellular matrix in all tissues. SLRPs bind to collagens and regulate collagen fibril growth and fibril organization. SLRPs also interact with various cytokines and extracellular compounds, which lead to various biological functions such cell adhesion and signaling, proliferation, and differentiation. Mutations in SLRP genes are associated with human diseases. Now crystal structures of five SLRPs are available. We describe some features of amino acid sequence and structures of SLRPs. We also review ligand interactions and then discuss the interaction surfaces. Furthermore, we map mutations associated with human diseases and discuss possible effects on structures by the mutations.

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References

Guidetti G, Bartolini B, Bernardi B, Tira M, Berndt M, Balduini C . Binding of von Willebrand factor to the small proteoglycan decorin. FEBS Lett. 2004; 574(1-3):95-100. DOI: 10.1016/j.febslet.2004.08.011. View

Zhou L, Hinerman J, Blaszczyk M, Miller J, Conrady D, Barrow A . Structural basis for collagen recognition by the immune receptor OSCAR. Blood. 2015; 127(5):529-37. PMC: 4742545. DOI: 10.1182/blood-2015-08-667055. View

Pal D, Chakrabarti P . Non-hydrogen bond interactions involving the methionine sulfur atom. J Biomol Struct Dyn. 2001; 19(1):115-28. DOI: 10.1080/07391102.2001.10506725. View

Scott P, McEwan P, Dodd C, Bergmann E, Bishop P, Bella J . Crystal structure of the dimeric protein core of decorin, the archetypal small leucine-rich repeat proteoglycan. Proc Natl Acad Sci U S A. 2004; 101(44):15633-8. PMC: 524833. DOI: 10.1073/pnas.0402976101. View

Matsushima N, Miyashita H, Mikami T, Kuroki Y . A nested leucine rich repeat (LRR) domain: the precursor of LRRs is a ten or eleven residue motif. BMC Microbiol. 2010; 10:235. PMC: 2946307. DOI: 10.1186/1471-2180-10-235. View

Ohta K, Aoyama E, Ahmad S, Ito N, Anam M, Kubota S . CCN2/CTGF binds the small leucine rich proteoglycan protein Tsukushi. J Cell Commun Signal. 2018; 13(1):113-118. PMC: 6381378. DOI: 10.1007/s12079-018-0487-x. View

Leroy B, Budde B, Wittmer M, De Baere E, Berger W, Zeitz C . A common NYX mutation in Flemish patients with X linked CSNB. Br J Ophthalmol. 2008; 93(5):692-6. DOI: 10.1136/bjo.2008.143727. View

Sui R, Li F, Zhao J, Jiang R . Clinical and genetic characterization of a Chinese family with CSNB1. Adv Exp Med Biol. 2008; 613:245-52. DOI: 10.1007/978-0-387-74904-4_28. View

Wang Q, Gao Y, Li S, Guo X, Zhang Q . Mutation screening of TRPM1, GRM6, NYX and CACNA1F genes in patients with congenital stationary night blindness. Int J Mol Med. 2012; 30(3):521-6. DOI: 10.3892/ijmm.2012.1039. View

10.

FORSIUS H, Damsten M, Eriksson A, Fellman J, Lindh S, Tahvanainen E . Autosomal recessive cornea plana. A clinical and genetic study of 78 cases in Finland. Acta Ophthalmol Scand. 1998; 76(2):196-203. DOI: 10.1034/j.1600-0420.1998.760215.x. View

11.

Khan A . Corneal ectasia in a boy with homozygous KERA mutation. Ophthalmic Genet. 2017; 39(1):141-143. DOI: 10.1080/13816810.2017.1350724. View

12.

Kanda R, Sutoh Y, Kasamatsu J, Maenaka K, Kasahara M, Ose T . Crystal structure of the lamprey variable lymphocyte receptor C reveals an unusual feature in its N-terminal capping module. PLoS One. 2014; 9(1):e85875. PMC: 3900441. DOI: 10.1371/journal.pone.0085875. View

13.

Tillgren V, Onnerfjord P, Haglund L, Heinegard D . The tyrosine sulfate-rich domains of the LRR proteins fibromodulin and osteoadherin bind motifs of basic clusters in a variety of heparin-binding proteins, including bioactive factors. J Biol Chem. 2009; 284(42):28543-53. PMC: 2781397. DOI: 10.1074/jbc.M109.047076. View

14.

Iozzo R, Buraschi S, Genua M, Xu S, Solomides C, Peiper S . Decorin antagonizes IGF receptor I (IGF-IR) function by interfering with IGF-IR activity and attenuating downstream signaling. J Biol Chem. 2011; 286(40):34712-21. PMC: 3186372. DOI: 10.1074/jbc.M111.262766. View

15.

Pang X, Dong N, Zheng Z . Small Leucine-Rich Proteoglycans in Skin Wound Healing. Front Pharmacol. 2020; 10:1649. PMC: 6997777. DOI: 10.3389/fphar.2019.01649. View

16.

Zarpellon A, Celikel R, Roberts J, McClintock R, Mendolicchio G, Moore K . Binding of alpha-thrombin to surface-anchored platelet glycoprotein Ib(alpha) sulfotyrosines through a two-site mechanism involving exosite I. Proc Natl Acad Sci U S A. 2011; 108(21):8628-33. PMC: 3102361. DOI: 10.1073/pnas.1017042108. View

17.

He X, Bazan J, McDermott G, Park J, Wang K, Tessier-Lavigne M . Structure of the Nogo receptor ectodomain: a recognition module implicated in myelin inhibition. Neuron. 2003; 38(2):177-85. DOI: 10.1016/s0896-6273(03)00232-0. View

18.

McEwan P, Scott P, Bishop P, Bella J . Structural correlations in the family of small leucine-rich repeat proteins and proteoglycans. J Struct Biol. 2006; 155(2):294-305. DOI: 10.1016/j.jsb.2006.01.016. View

19.

Kalamajski S, Oldberg A . Homologous sequence in lumican and fibromodulin leucine-rich repeat 5-7 competes for collagen binding. J Biol Chem. 2008; 284(1):534-539. DOI: 10.1074/jbc.M805721200. View

20.

Zeitz C, Robson A, Audo I . Congenital stationary night blindness: an analysis and update of genotype-phenotype correlations and pathogenic mechanisms. Prog Retin Eye Res. 2014; 45:58-110. DOI: 10.1016/j.preteyeres.2014.09.001. View